Zhongshan Hospital affiliated to Fudan University, Shanghai, China.
Viet-Duc Hospital, Hanoi, Viet Nam.
Int J Antimicrob Agents. 2017 May;49(5):579-588. doi: 10.1016/j.ijantimicag.2017.01.010. Epub 2017 Mar 29.
Ceftazidime/avibactam comprises the broad-spectrum cephalosporin ceftazidime and the non-β-lactam β-lactamase inhibitor avibactam. This phase 3, randomised, double-blind study (NCT01726023) assessed the efficacy and safety of ceftazidime/avibactam plus metronidazole compared with meropenem in patients with complicated intra-abdominal infection (cIAI) in Asian countries. Subjects aged 18-90 years and hospitalised with cIAI requiring surgical intervention were randomised 1:1 to receive every 8 h either: ceftazidime/avibactam (2000/500 mg, 2-h infusion) followed by metronidazole (500 mg, 60-min infusion); or meropenem (1000 mg, 30-min infusion). Non-inferiority of ceftazidime/avibactam plus metronidazole to meropenem was concluded if the lower limit of the 95% confidence interval (CI) for the between-group difference in clinical cure rate was greater than -12.5% at the test-of-cure (TOC) visit (28-35 days after randomisation) in the clinically evaluable (CE) population. Safety was also evaluated. Of 441 subjects randomised, 432 received at least one dose of study medication (ceftazidime/avibactam plus metronidazole, n = 215; meropenem, n = 217). In the CE population at the TOC visit, non-inferiority of ceftazidime/avibactam plus metronidazole to meropenem was demonstrated, with clinical cure reported for 93.8% (166/177) and 94.0% (173/184) of subjects, respectively (between-group difference, -0.2, 95% CI -5.53 to 4.97). The clinical cure rate with ceftazidime/avibactam plus metronidazole was comparable in subjects with ceftazidime-non-susceptible and ceftazidime-susceptible isolates (95.7% vs. 92.1%, respectively). Adverse events were similar between the study groups. Ceftazidime/avibactam plus metronidazole was non-inferior to meropenem in the treatment of cIAIs in Asian populations and was effective against ceftazidime-non-susceptible pathogens. No new safety concerns were identified.
头孢他啶/阿维巴坦由广谱头孢菌素头孢他啶和非β-内酰胺β-内酰胺酶抑制剂阿维巴坦组成。这项 3 期、随机、双盲研究（NCT01726023）评估了头孢他啶/阿维巴坦联合甲硝唑与美罗培南治疗亚洲国家复杂性腹腔内感染（cIAI）患者的疗效和安全性。年龄在 18-90 岁之间、因 cIAI 需要手术干预而住院的患者按 1:1 随机接受每 8 小时一次的治疗：头孢他啶/阿维巴坦（2000/500mg，2 小时输注），随后给予甲硝唑（500mg，60 分钟输注）；或美罗培南（1000mg，30 分钟输注）。如果临床治愈率的组间差异的 95%置信区间（CI）下限在治疗结束时（随机后 28-35 天）在可临床评估（CE）人群中大于-12.5%，则可得出头孢他啶/阿维巴坦联合甲硝唑不劣于美罗培南的结论。还评估了安全性。在 441 名随机患者中，432 名至少接受了一剂研究药物（头孢他啶/阿维巴坦联合甲硝唑，n=215；美罗培南，n=217）。在治疗结束时的可临床评估人群中，头孢他啶/阿维巴坦联合甲硝唑与美罗培南相比显示出非劣效性，分别有 93.8%（166/177）和 94.0%（173/184）的患者报告了临床治愈（组间差异，-0.2，95%CI-5.53 至 4.97）。头孢他啶/阿维巴坦联合甲硝唑治疗头孢他啶不敏感和头孢他啶敏感分离株的临床治愈率相似（分别为 95.7%和 92.1%）。两组的不良事件相似。头孢他啶/阿维巴坦联合甲硝唑在亚洲人群中治疗复杂性腹腔内感染不劣于美罗培南，对头孢他啶不敏感的病原体有效。未发现新的安全性问题。
